The Final Frontier - the human brain

In attempting to develop a treatment for fibromyalgia, Jeff Hargrove has entered the last frontier of medicine - the human brain.

Two years ago Dr. Jeff Hargrove, associate professor of Mechanical Engineering at Kettering University and adjunct assistant professor of Internal Medicine at Michigan State University, launched a collaborative effort to develop a diagnostic tool and viable course of treatment for fibromyalgia, a disease believed to be caused by neurochemical imbalances arising from abnormal brain function. The illness is characterized by debilitating full body diffuse pain, cognitive dysfunction and sleep disorders.

In the next few months he will begin the actual treatment phase of a clinical trial to study the effects of low-intensity electrical neurostimulation on fibromyalgia patients. The study will also investigate the effect on myofascial trigger points that arise from a condition different than fibromyalgia but commonly occurring at the same time. Myofascial trigger points are a common cause of muscle pain symptoms. The treatment being investigated involves sending a small electrical impulse into the brain to stimulate the brain to function normally. The impulse is so slight it cannot be felt during treatment.

"We are a year behind schedule due to the loss of one of our original researchers," said Hargrove, "and the need for part-time technicians who can make a two-year commitment to the project. That seems to be behind us now, so we're moving ahead as fast as possible."

Working with Hargrove are co-investigators Susan Smith, MD, and Sunil Nagpal, MD, both of McLaren Regional Medical Center's Internal Medicine Department; Don Deering, Ph.D. (ca), an expert in EEG and neurostimulation techniques; and David Simons, MD, of Atlanta, an expert in muscle anatomy and muscle pain.

About 360 people have applied to be part of the clinical trial. "We will be choosing 160 to participate," Hargrove said. "We have already enrolled the first 20 of the 160, and will resume examinations forthe remaining 140 very soon. So far we see that about 40 percent of everybody we examine will not qualify for the study, mainly because they have been misdiagnosed in the first place. This is a common problem with this illness."

Once enrolled, participants will have a Quantitative Electroencaphalograph (QEEG) to map brain functions and enable the researchers to begin topographical analysis. The QEEG gives a comprehensive picture of activity at 19 points in the brain simultaneously and how various points correspond to one another.

Another advantage to using the QEEG is to be able to compare results to existing normative databases. "When we began the study we were going to collect EEG from 19 areas of the brain using one site on the scalp at a time. Introducing QEEG gives us some far more advanced capability. This will give us a better idea how, if at all, fibromyalgia patients brain functions differ from a 'healthy normal person's' brain function," said Hargrove. "When we can assess how they differ, we can better understand the illness and devise better treatment protocols."

Following the QEEG phase, actual treatment will begin within a month. The clinical trial will wrap up about two years after the treatment phase starts, Hargrove said.

As is common in research, Hargrove has made ancillary discoveries trying to unravel fibromyalgia, which have helped develop new research projects.

The first is a need to study the breathing patterns of fibromyalgia patients. "The fundamentals of health are blood flow and oxygenation," Hargrove said. "Fibromyalgia patients have a number of symptoms consistent with those suffered by people experiencing chronic respiratory problems. They have also been shown to exhibit reduced regional cerebral blood flow, meaning the brain isn't getting enough blood in certain areas. And reduced blood flow means reduced oxygen," he said.

According to Hargrove, 'healthy', non-fibromyalgia sufferers, demonstrate a relatively consistent breathing pattern due to careful central nervous system coordination of the primary muscles of respiration. These muscles include the diaphragm, the intercostals between the ribs and neck muscles including the scalenes and the sternocleidomastoid. In order for us to breathe properly, all of these muscles must work together efficiently and with proper timing, every few seconds of our life. By measuring and carefully analyzing how the chest and abdomen move during breathing, researchers develop a base of 'normal' breathing patterns that allow clinicians to tell whether or not the muscles of respiration are working properly when respiratory dysfunction is present.

"Our research is exploring what could be happening to alter the oxygenation of tissues," said Hargrove. "There has been very little research looking at the breathing patterns of fibromyalgia patients and we think this could be a very important piece of the puzzle."

For example, fibromyalgia patients often have what is called a paradoxical breathing pattern, where their abdomen doesn't go out when they inhale, it goes in. In normal breathing the abdomen goes out during inhalation as the diaphragm pushes down creating an increase in pressure on the lower abdomen. The upper chest should also rise slightly during normal inhalation. With paradoxical breathing, the diaphragm does not push down effectively, leaving the neck and shoulder muscles to do excessive work in opening the lung area to allow oxygen in.

Hargrove explained that considering paradoxical breathing alone, several common symptoms of fibromyalgia may be partially explained. For example, fibromyalgia sufferers commonly have irritable bowel syndrome and experience a lot of neck and shoulder pain. In terms of the bowel problems, the rhythmic pulse of pressure from proper diaphragmatic breathing is not present in paradoxical breathing. This pressure pulse is vital to proper "flow". Further, the neck and shoulder muscles are not made to be constantly overused. They cannot metabolize nutrients fast enough and eventually become sore and stiff from doing all the work of breathing. As this happens, it becomes more difficult to take a deep breath and thus fully oxygenate the blood. When the ability to take in oxygen is diminished, the blood carbon dioxide level is affected as well, leading to an increase in blood and tissue pH. This increased level of alkalinity makes it difficult for the body to release oxygen from the blood into muscle and other organ tissues, resulting in a vicious cycle that would likely result in muscle pain, fatigue, sleep problems and cognitive difficulty, all hallmark symptoms of fibromyalgia.

"We think fibromyalgia is an outcome of one or more long unresolved physical conditions including head injury, infection and stress, and that the brain is in some form of chronic protective mode," said Hargrove.

"Bad breathing patterns are often habitual and may be very relevant in the disease process of fibromyalgia. They could be an underlying physical condition of fibromyalgia," he said. "Changing breathing patterns could address the root cause of fibromyalgia for some patients, or at least be part of a series of conditions that perpetuate the problem and prevent the body from healing."

Another spin-off from this research is the development of a new way of recording the location and severity of a fibromyalgia patient's pain based on their input to a computerized pain patterns chart. Hargrove developed software that makes it easier for a patient to give physicians a more detailed analysis of what's going on, where it hurts and how badly it hurts. "I have completed a validation study on that and we'll be using it in the fibromyalgia study too," he said.

For more information about the fibromyalgia research of Dr. Hargrove, visit his research study website at www.fm-research.com.